Many imidazoquinoline amine, imidazopyridine amine, 6,7-fused cycloalkylimidazopyridine amine, imidazonaphthyridine amine, tetrahydroimidazonaphthyridine amine, oxazolopyridine amine, oxazoloquinoline amine, thiazolopyridine amine, thiazoloquinoline amine and 1,2-bridged imidazoquinoline amine immune response modifiers are known. These compounds are hereinafter sometimes referred to as immune response modifying compounds (IRMs). Such compounds, methods for preparing them, formulations containing them and methods of using them are disclosed in, for example, U.S. Pat. Nos. 4,689,338; 5,389,640; 5,268,376; 4,929,624; 5,266,575; 5,352,784; 5,494,916; 5,482,936; 5,395,937; 5,238,944; 5,175,296; 5,693,811; 5,741,908; 5,756,747; 5,939,090; 6,110,929; 4,988,815; 5,376,076; 6,083,505; 6,039,969; and PCT Publications WO 99/29693, WO 00/40228, WO 00/76505, WO 00/76518 and WO 00/76518.
The IRM compounds have demonstrated antiviral and antitumor activity. The antiviral and antitumor activity is not direct but is believed to result from their ability to stimulate an innate immune response. In cultures of human peripheral blood mononuclear cells, members of this class of compounds have been shown to stimulate the production and release of a variety of cytokines and chemokines including interferon-α, tumor necrosis factor-α, interleukin-1 (IL-1), IL-1 receptor antagonist, IL-6, IL-8, IL-12, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein (MIP-1α).
In addition to stimulating an innate immune response, the IRM compounds have been found to mediate the acquired immune response. In human peripheral blood mononuclear cell cultures, members of this class of compounds have been shown to induce the production of the T helper type 1 (TH1) cytokine interferon-γ and to inhibit the production of T helper type 2 (TH2) cytokines IL-4 and IL-5.
One of these IRM compounds, known as imiquimod (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine), has been commercialized in a topical formulation, Aldara™ cream, for the treatment of anogenital warts associated with human papillomavirus. Imiquimod is also being evaluated in clinical trials for use in treating superficial basal cell carcinoma and actinic keratosis.
Another of these IRM compounds, known as resiquimod (4-amino-2-ethoxymethyl-α,α-dimethyl-1H-imidazo[4,5-c]clinical trials for use in preventing genital herpes recurrences.
There are numerous venomous flora and fauna in the world, some of which possess venom that causes significant medical problems when a human or an animal is exposed to the venom. Envenomation by such a plant or animal can cause both systemic and local reactions. Examples of local reactions include edema, erythema, induration, necrotic ulcers, pain, pruritis, and vesicles. The severity of the reaction is dependent on a variety of factors including the source of the venom (e.g. Loxosceles spider, box jellyfish, fire ant), the amount of venom injected, the location of the bite or sting (e.g. arm, thigh), and prior exposure to the venom. A variety of treatments have been used including analgesics, antibiotics, antivenoms, corticosteroids, Dapsone, and hyperbaric oxygen. In those instances where the initial dermal lesion progresses to dermonecrosis, surgical intervention is often necessary. There is a continuing need for new treatments and in particular for treatments that will prevent dermonecrosis.